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Cytokine. 2014 Dec;70(2):126-33. doi: 10.1016/j.cyto.2014.06.020. Epub 2014 Jul 26.

IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor.

Author information

1
Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA; Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, MO 65212, USA. Electronic address: nichollm@health.missouri.edu.
2
Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA.
3
Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA; Department of Surgery, Luohu Hospital, Shenzhen, China.
4
Department of Surgery, University of Missouri School of Medicine, Columbia, MO 65212, USA; Department of Obstetrics & Gynecology, Luohu Hospital, Shenzhen, China.
5
Department of Pathology, University of Missouri School of Medicine, Columbia MO 65212, USA.
6
Department of Microbiology & Immunology, Des Moines University College of Osteopathic Medicine, Des Moines, IA 50312, USA. Electronic address: yujiang.fang@dmu.edu.

Abstract

Interleukin-35 (IL-35), an IL-12 cytokine family member, mediates the immune inhibitory function of regulatory T cells (Treg). We assayed the presence of IL-35 in paraffin-embedded human pancreas cancer (PCAN) and unexpectedly found IL-35 was expressed mainly by epithelial derived PCAN cells, but not by Treg. We further examined the expression and effect of exogenous IL-35 in human PCAN cell lines and found IL-35 promoted growth and inhibited apoptosis in PCAN cell lines. IL-35 induced proliferation correlated with an increase in cyclin B, cyclin D, cdk2, and cdk4 and a decrease in p27 expression, while inhibition of apoptosis was associated with an increase in Bcl-2 and a decrease in TRAILR1. We conclude IL-35 is produced by PCAN in vivo and promotes PCAN cell line growth in vitro. These results might indicate an important new role for IL-35 as an autocrine growth factor in PCAN growth.

KEYWORDS:

Apoptosis; IL-35; Pancreatic cancer; Proliferation

PMID:
25073578
DOI:
10.1016/j.cyto.2014.06.020
[Indexed for MEDLINE]

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